Autoimmune Thyroiditis in Childhood

Autoimmune thyroiditis (AIT) is the most common thyroid disorder in the pediatric age range. The disease results from an as yet poorly characterized defect or defects in immunoregulation and a cascade of events progressing from lymphocyte infiltration of the thyroid, to T-cell- and cytokine-mediated thyroid follicular cell injury, and apoptotic cell death. Approximately 70% of disease risk has been attributed to genetic background with environmental factors being important in triggering disease in susceptible individuals. The contribution of individual genes is small and probably polymorphisms in multiple genes play a role. Some immunosusceptibility genes affect immune recognition or response in general, while others are thyroid-specific. Environmental agents may act through an epigenetic mechanism. Antibodies (Abs) to a variety of thyroid-specific antigens are detectable in a majority of patients, but the role of Abs in mediating cell injury and death is unclear and only thyrotropin (TSH) receptor Abs significantly affect thyroid function by interfering with (or stimulating) the action of TSH. Nonetheless, thyroid peroxidase (TPO) Abs and thyroglobulin (Tg) Abs, present in a majority of patients, are valuable diagnostically as markers of underlying autoimmune thyroid destruction. TSH receptor blocking Abs are found in ˜18% of children and adolescents with severe hypothyroidism and, when persistent, may identify an adolescent likely to have a baby with TSH receptor blocking Ab-induced congenital hypothyroidism. AIT may coexist with other organ-specific autoimmune diseases. Although the most common age at presentation is adolescence, the disease may occur rarely in children <1 year of life. Conflict of interest:None declared

Laughing at or with the text?

This study of text/image relations in manuscripts of Burgundian prose romances illuminated by the Wavrin Master analyses how the verbal comedy of the narrative is represented visually. Whether this is through direct pictorial equivalents to amusing episodes in the text or “translation” of these episodes into the visual language of clothing, gesture and symbolism, the illuminator can be shown to be faithful to the narrative in deploying comedy for the didactic instruction of the reader/viewer.L’examen des rapports texte/image dans les manuscrits de romans bourguignons en prose illustrés par le Maître de Wavrin révèle les moyens dont il use pour représenter dans ses miniatures la comédie verbale du texte. Que ce soit en fournissant un équivalent pictural des épisodes comiques du récit ou en « traduisant » ces épisodes en langage visuel selon des codes vestimentaires, gestuels ou symboliques, l’artiste est fidèle au texte en provoquant le rire chez le lecteur/spectateur tout en l’instruisant

Role of activity in neuromuscular synaptic degeneration: insights from Wlds mice

The nervous system is a dynamic structure. Both during development and in the adult, synapses display activity-dependent plasticity which can modify their structure and function. In the neonate, activity influences the stability of functional connections between the muscle and nerve. In adults, the process of neurotransmitter release and the structure of the postsynaptic muscle can also be altered by external stimuli such as exercise. It is important to understand this plasticity of the neuromuscular system, the ways in which it can be modified, and its relationship to the maintenance or degeneration of synapses. After injury, peripheral nerve undergoes Wallerian Degeneration, during which the connections between axons and muscle fibres are lost, followed by the fragmentation of the nerve itself. The primary goal of this thesis was to determine whether activity modulates this process; that is, whether enhancing or reducing neuromuscular activity creates a susceptibility to degeneration or alternatively provides any protection against it. Developing greater understanding of this process is essential in relation to neurodegenerative disorders in which the benefits of activity, in the form of exercise, are controversial. Using Wlds mice, in which synaptic degeneration occurs approximately ten times more slowly than normal after nerve injury, I investigated the influence of both decreased (tetrodotoxin induced paralysis) and increased (voluntary wheel running) activity in vivo on this process. Paralysis prior to axotomy resulted in a significant increase in the rate of synapse degeneration. Using a novel method of repeatedly visualising degenerating synapses and axons in vivo I also established that this effect was specific to the synapse, as it did not affect the degeneration of axons. In contrast, voluntary wheel running had no effect on the rate of either axonal or neuromuscular synapse degeneration, but induced a slight modification of neuromuscular transmission. To provide a more stringent test I developed a novel assay based on overnight, ex vivo incubation of nerve-muscle preparations at 32°C. I first demonstrated that this procedure separates the different degeneration time courses for neuromuscular synapse degeneration in wild-type and Wlds preparations. I then extended the study to investigate further ways of modulating synaptic degeneration. First, I tested the effects of electrical stimulation. Intermittent high frequency (100Hz) stimulation reduced the level of protection. Finally, I tested the effects of NAMPT enzymatic inhibitor FK866 on synaptic degeneration. Interestingly, the synaptic protection observed in Wlds muscles was enhanced in the presence of FK866. The results of my findings are relevant to understanding the plasticity of synapses and its relationship to degeneration. Together, these studies highlight the potential of genetic and epigenetic factors, including activity, to regulate neuromuscular synapse degeneration. My study also provides proof of concept for a novel organotypic culture system in which to identify pharmacological modulators of synaptic degeneration that could form part of a second-line screen for neuroprotective compounds or phenotypes. My findings may be viewed in the wide context of neurodegenerative disease, since synaptic use or disuse is widely thought to influence susceptibility, onset and progression in such disorders

Practice, a Novel; and Discipline Your Darlings: Writerly Discipline in Freud, Foucault, and the Discourses of Creative Writing

This thesis explores, in both creative and critical modes, the concept of discipline and its relationships to desire, attention, creativity and writing. The creative component, a novel entitled Practice, follows its protagonist, Annabel, through a day in the strictly routinised life she has designed to maximise her own immersion in her undergraduate work. As she reads, walks, and fantasises, the various threads of her thinking–her work on Shakespeare’s sonnets, her relationship with her older boyfriend Rich, and her own private story about two invented characters–begin to tangle together in a contrapuntal meditation on obsession, distraction, and eroticism. The critical component identifies and examines the contemporary cultural fascination with ‘writerly discipline’, the expectation that writers must consciously design and regulate their own working practices to produce good work. I begin with a theoretical introduction to discipline, demonstrating that it is conceptually unstable and depends on its underlying ‘doctrine’ for its ideological significance. My first chapter then analyses a corpus of recent Anglo-American texts which speak to the theme of writerly discipline; these sources place discipline in ambivalent interrelation with an assumed innate personal creativity which is supposed to be necessary for creative writing but also to require constant management. My second chapter, picking up on Freudian themes in my corpus of modern sources, explores Freud’s own discussions of self-discipline and creative writing, demonstrating that they are liable to some of the same contradictions and ambivalences as more recent discourses. In my final chapter I use the work of Michel Foucault to extend my critique of discourses of writerly discipline, concluding that–as Foucault suggests of sexuality–creativity may well be conceptually constituted, rather than ‘discovered’, by discourses about how to access and manage it. The creative component of this thesis has been omitted from the publicly available version

Generation X and Y : a comparative analysis of entrepreneurial intent

Entrepreneurs are seen to play a vital role in the growth of an economy, particularly in an emerging market such as South Africa. To date, there has been a limited amount of research concerning the drivers, influences and factors that predispose an individual towards entrepreneurial intent within the South African context. Equally so, there is little research on generational theory and how this relates to entrepreneurial activity as a whole. This study focuses on comparing the X and Y generational cohorts in terms of their propensity towards entrepreneurial intent within the context of South Africa. Research was conducted following an in depth literature review which focused on the concept of entrepreneurship and its effect on the economy, generational theory and the interaction and influence of generational cohort theory on the drivers of entrepreneurial intent. The data gathered through the course of the literature review was utilised as a theoretical foundation on which to build propositions of entrepreneurial intent and from which a quantitative survey instrument was developed. The quantitative survey was open to any South African individual who falls within the X or Y generational cohort as defined in this study.Key findings include similarities and differences between the X and Y generational cohort individuals in terms of the following aspects: education and entrepreneurial training; exposure to technology; problem solving; leadership orientation; visionary perspective; the influence of family and organisational support networks; creativity and innovation, attitude towards risk-taking and self-confidence. It is hoped that the findings contribute to the existing literature on entrepreneurial intent and in particular to that within the South African context of the X and Y generational cohorts. CopyrightDissertation (MBA)--University of Pretoria, 2010.Gordon Institute of Business Science (GIBS)unrestricte

Fraternité et chevalerie dans la version bourguignonne de "Florence de Rome" (Chantilly, Bibliothèque du château, ms. 652)

Résumé La séparation entre arma et amor que nous pouvons constater dans les récits de chevalerie du XVe siècle amène les auteurs de ces textes à s?interroger autant sur les relations entre les chevaliers eux-mêmes que sur celles entre le chevalier et sa dame. En particulier, les liens unissant des chevaliers qui sont également des frères font l?objet de plusieurs romans de l?époque, comme par exemple la mise en prose bourguignonne de Florence de Rome, où les deux frères Milon et Esmeré, jeunes chevaliers hongrois, se disputent la main de l?héroïne éponyme. Dans la version de ce récit illustrée par l?artiste surnommé le « Maître de Wavrin » (Chantilly, Bibliothèque du château, ms. 652), les tensions entre fraternité et chevalerie passent au premier plan ? dans le texte comme dans les images ? jusqu?à prendre toute une dimension éthique et politique. Comme nous le verrons, la façon dont les deux frères se comportent entre eux en dit long sur leur aptitude à mériter non seulement l?amour de la dame, mais le gouvernement d?un royaume entier, livrant ainsi une leçon à la fois poignante et incisive sur les m?urs chevaleresques à la fin du Moyen Âge. Abstract  The separation of arma and amor that can be found in the chivalric tales of the fifteenth century allows the authors of these works to devote as much attention to the relationships between knights as to those between a knight and his lady. In particular, the bonds between knights who are also brothers are examined in various texts of the period, such as the Burgundian prose reworking of Florence de Rome, in which the brothers Milon and Esmeré, two young knights from Hungary, vie with each other for the hand of the eponymous heroine. In the version of this romance illustrated by the artist known as the « Wavrin Master » (Chantilly, Bibliothèque du château, ms. 652) the tensions between brotherhood and knighthood are foregrounded in both the narrative and its accompanying miniatures to the extent of taking on a political and ethical dimension. As I argue here, the way in which the two brothers act towards each other can be seen as an indicator of their suitability not only as the lady?s prospective husband but also as the future ruler of a realm, thus providing a trenchant and incisive lesson on chivalric mores at the end of the Middle Ages

Adolescence, anxiety and amusement in versions of Paris et Vienne

Idyllic romances such as Paris et Vienne, which exists in three different versions, explore the tensions created by depicting young lovers in conflict with their parents on the issue of whom they want to marry. Whilst the original version, as preserved in Paris, BnF fr. 1480, uses comedy in order to present the hero and heroine as tricksters whose flouting of parental authority evokes ambivalence in the reader, the Burgundian redaction (Brussels, KBR 9632/3) reduces this emphasis on the couple’s duplicitousness by ending the tale with a lengthy retrospective validation of Paris as chivalric hero and true aristocrat. By contrast, the shorter version of Paris et Vienne, which is extant in Paris, BnF fr. 20044, largely strips the narrative of its capacity to amuse and extracts from the tale an uncompromisingly serious message about the moral dilemmas and emotional anguish undergone by young lovers intent on pursuing their personal desires.Les romans idylliques, tels que celui de Paris et Vienne, qui existe en trois rédactions différentes, explorent les tensions créées lorsque deux jeunes amants s’opposent à la volonté de leurs familles en matière de mariage. Alors que la version originale (e.g. Paris, BnF fr. 1480) utilise l’humour afin de peindre les amants sous les traits de trompeurs, effet qui n’aurait pas manqué de susciter une certaine ambivalence chez le lecteur médiéval, la rédaction bourguignonne (Bruxelles, KBR 9632/3) essaie de modifier cette impression du couple en ajoutant à la fin du récit une longue justification rétrospective de la prouesse et de la noblesse du héros. En revanche, la version plus courte de l’histoire (Paris, BnF fr. 20044) élimine la plus grande partie de l’humour du texte original afin d’en tirer une leçon morale de portée plus sérieuse sur les angoisses subies par les amants en quête de leur propre destin affectif